Atypical antipsychotic

The first atypical antipsychotic medication, clozapine was discovered in the 1950's, and introduced in clinical practive cin the 1970's, however it fell out of popularity due to concerns over drug induced agranulocytosis. Despite the effectiveness of clozapine for treatment resistant schizophrenia, agents with a more favorable side effect profile were necessary for widespread use. During the 1990s, olanzapine, risperidone, and quetiapine were introduced, with ziprasidone and aripirazole following in the early 2000's. The atypical antipsychotics have found favor among clinicians and are now considered to be first line treatments for schizophrenia and are gradually replacing the typical antipsychotics. Most researchers agree that the defining characteristic of an atypical antipsychotic is the decreased propensity of these agents to cause extrapyramindal side effects and to elevate prolactin levels.

Pharmacology of the Atypicals

There is debate over the pharmacology that is responsible for the unique profile of atypical antipsychotics. Some researchers believe that Dopamine 2 receptor antagonism, coupled with serotonin 2A receptor antagonism, is responsible for the "atypicality" of atypical antipsychotics. Others believe that fast dissociation (a fast Koff) from the D2 receptor, allowing for better transmission of normal physiological dopamine surges, better explains the pharmacological evidence.

Metabolic Concerns with Atypical Antipsychotics

Recently, metabolic concerns have been of grave concern to clinicians, patients and the FDA. In 2003, the FDA required all manufacturers of atypical antipsychotics to change their labeling to include a warning about the risks of hyperglycemia and diabetes with atypical antipsychotics. It must also be pointed out that all though all atypicals must carry the waring on their labeling, data shows that all atypicals are not equal in their effects of weight and insulin sensitivity. The general consensus is that clozapine and olanzapine are associated with the greatest metabolic risks, followed by risperidone, and quetiapine in no particular order. Ziprasidone and aripiprazole are thought to have the smallest effects on weight and insulin resistance, but clinical experience with these newer agents is less than that with the older agents.

The issue of metabolic side effects, such as hyperglycemia, with these medicaitons is somewhat clouded by the fact that schizophrenics seem to have an increased incidence of impaired glucose metabolism, even without the presence of these antipsychotic agents. The question is whether the increased risk for diabetes and hyperglycemia a functino fo the disease state of schizophrenia, or can these metabolic effects be blamed on the drugs completely. It is probably a combination of both these factors that are responsible for the observations of increased adverse metabolic events in patients taking atypical antipsychotics.

The atypical antipsychotics are believed to be better at treating the "negative symptoms" of schizophrenia. In the atypical medications, the risk of tardive dyskinesia is lower, however, weight-gain is more common in many, but not all, of the atypical medications.

Atypical medications

• Clozapine (Clozaril^®)
• Olanzapine (Zyprexa^®)
• Quetiapine (Seroquel^®)
• Risperidone (Risperdal^®)
• Ziprasidone (Geodon^®)
• Aripiprazole (Abilify^®)
• Sertindole (Serlect^®, Serdolect^®) (Not approved by the FDA for use in the USA)